Floriana Zennaro

Chronic inflammation in congenital cystic adenomatoid malformations. An underestimated risk factor

PURPOSE Congenital cystic malformations of the lung are more frequently diagnosed before birth, but guidelines for surgical management of asymptomatic cases are lacking. The aim of this article is to review our 10-year results with antenatally diagnosed congenital cystic adenomatoid malformations (CCAMs) to debate indications for early postnatal surgical management in asymptomatic patients. METHOD Twenty-four cases were reviewed; of these, 18 were operated on before 15 days of life for respiratory distress or mediastinal shift, whereas 6 were submitted to elective surgery at 3 months of age. RESULTS Twenty lobectomies and 4 atypical resections were performed. Two of the latter required a second surgery for incomplete primary perinatal resection. No postsurgical complications were reported. Nineteen (19/24) of the resected specimens showed signs of chronic inflammation. In the perinatal period, 100% (8 cases) of CCAM type II and 50% (8 cases) of CCAM type I resulted to be inflamed. Of the asymptomatic cases, 50% (3/6) were also found to be affected. No infections were detected at bacteriologic culture and bacterial debris was stained in 3 specimens. CONCLUSION In this series, a 79% incidence of pulmonary inflammation was detected. The CCAM type II resulted to be always involved in this process of inflammation. This was an unexpected finding, particularly in cases without mediastinal shift or respiratory distress. In light of these results, early postnatal treatment, at around 3 to 6 months of age, could be considered even in asymptomatic patients.

Propranolol for Cerebral Cavernous Angiomatosis A Magic Bullet

A little girl, born at term with normal perinatal history, experienced at the age of 10 months an enduring seizure without fever or other clinical remarks of any infective disease. Neurological examination showed right hemiparesis. Magnetic resonance imaging (MRI) revealed numerous intracranial lesions with hemorrhagic features, consistent with multiple small cavernous angiomas. She was treated with antiepileptic drug (levetiracetam 150 mg × 2 per day) and in the following months never suffered from other seizures. Despite her good physical conditions, further MRIs showed a worsening of radiological imaging, with increasing size and perilesional hemorrhage (Figure 1). At the age of 15 months, she was evaluated in our department where the diagnosis of cerebral angiomatosis was confirmed and a treatment with propranolol was started at the dosage of 2 mg/kg/d divided in 3 doses. After 1 month of treatment MRI showed a significant reduction in many brain lesions and 2 months later the result was impressive (Figure 2). Her electrocardiogram was normal at each control and she never showed any side effects possible related to propranolol. She has been treated with propranolol for 6 months. At the end of therapy, MRI was stably improved showing further improvement 6 months after treatment discontinuation. Cavernous angiomas are occult vascular malformations that affect 0.4% to 0.9% of the population. They can be single or multiple, sporadic or familial. The presence of multiple lesions is more common in familial cavernomatosis. Intracranial cavernous angiomas can be asymptomatic, but the fragile vessels predisposes to hemorrhage, often responsible of clinical symptoms as headaches, seizures, focal neurological signs. Because of the potential de novo formation and rapid enlargement of existing lesions, children with intracranial cavernous angiomas need to be followed carefully and regularly. In case of bleeding, symptoms are likely to be self-limiting, but further hemorrhages are possible, so that a surgical approach in often needed, also because the lesions do not involve spontaneously over time. Even if intracranial cavernous angiomas are not identical to infantile hemangiomas and though there is only one case report in the literature regarding propranolol treatment for brain cavernoma, we administered 492885 CPJXXX10.1177/0009922813492885Clinical Pediatrics XX(X)Berti et al research-article2013

Es eficaz el tratamiento con hidroxicloroquina en el déficit de proteína C surfactante

We present the case of two twin brothers with surfactant protein C deficiency who were treated with hydroxychloroquine for three years, with apparent success. The exact physiopathology of this disease is not known and there is no specific treatment for it. There is merely news from a few previous descriptions in the literature about the use of hydroxychloroquine for surfactant protein C deficiency with satisfactory results. Two years after the treatment was withdrawn, the twins were evaluated once again: they presented no new infections, growth and general state were normal and chest CT showed a notable additional reduction in the interstitial pneumopathy. These data seem to cast some doubt on the efficacy of hydroxychloroquine, and they suggest that the clinical improvement was simply the natural evolution of the disease.

RICH (Rapidly Involuting Congenital Hemangioma): Not only a definition of wealth

e describe the case of a newborn female infant, born at term with a birth weight of 3750 g via uncomplicated vaginal delivery. On physical examination, a 54-cm, round, firm violaceous lesion surrounded by a pale halo was present on the left shoulder (Figure, A). This lesion had not been detected by prenatal ultrasound. Ultrasonographic examination at birth showed a superficial mass, mostly confined to the subcutaneous tissue, uniformly hypoechoic, with a hyperechoic edge. The lesion

An Update on the Pathogenesis and Treatment of Chronic Recurrent Multifocal Osteomyelitis in Children.

Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic non-bacterial osteomyelitis (CNO), is a rare inflammatory disorder that primarily affects children. It is characterized by pain, local bone expansion, and radiological findings suggestive of osteomyelitis, usually at multiple sites. CRMO predominantly affects the metaphyses of long bones, but involvement of the clavicle or mandible are suggestive of the diagnosis. CRMO is a diagnosis of exclusion, and its pathogenesis remains unknown. Differential diagnosis includes infection, malignancies, benign bone tumors, metabolic disorders, and other autoinflammatory disorders. Biopsy of the bone lesion is not often required but could be necessary in unclear cases, especially for differentiation from bone neoplasia. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment. Alternative therapies have been used, including corticosteroids, methotrexate, bisphosphonates, and tumor necrosis factor (TNF)-α inhibitors. No guidelines have been established regarding diagnosis and treatment options. This manuscript gives an overview of the most recent findings on the pathogenesis of CRMO and clinical approaches for patients with the condition.

Real-time tele-mentored low cost "Point-of-Care US" in the hands of paediatricians in the emergency department: Diagnostic accuracy compared to expert radiologists

Background The use of point-of-care ultrasonography (POC US) in paediatrics is increasing. This study investigated the diagnostic accuracy of POC US in children accessing the emergency department (ED) when performed by paediatricians under the remote guidance of radiologists (TELE POC). Methods Children aged 0 to 18 years accessing the ED of a third level research hospital with eight possible clinical scenarios and without emergency/severity signs at the triage underwent three subsequent US tests: by a paediatrician guided remotely by a radiologist (TELE POC); by the same radiologist (UNBLIND RAD); by an independent blinded radiologist (BLIND RAD). Tele-radiology was implemented using low cost “commercial off-the-shelf” (COTS) equipment and open-source software. Data were prospectively collected on predefined templates. Results Fifty-two children were enrolled, for a total of 170 ultrasound findings. Sensitivity, specificity, positive and negative predictive values of TELE POC were: 93.8, 99.7, 96.8, 99.4 when compared to UNBLIND RAD and 88.2, 99.7, 96.8, 98.7 when compared to BLIND RAD. The inter-observers agreement between the paediatricians and either the unblind or blind radiologist was excellent (k = 0.93). The mean duration of TELE POC was 6.3 minutes (95% CI 4.1 to 8.5). Technical difficulties occurred in two (3.8%) cases. Quality of the transmission was rated as fair, good, very good and excellent in 7.7%, 15.4%, 42.3% and 34.6% of cases respectively, while in no case was it rated as poor. Conclusions POC US performed by paediatricians in ED guided via tele-radiology by an expert radiologist (TELE POC) produced reliable and timely diagnoses. Findings of this study, especially for the rarer conditions under evaluation, need further confirmation. Future research should investigate the overall benefits and the cost savings of using tele-ultrasound to perform US “at children’s bedsides”, under remote guidance of expert radiologists.

A case of Rubinstein‐Taybi syndrome associated with growth hormone deficiency in childhood

Dear Editors, Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant disease. Point mutations or deletions of the cAMPresponse element-binding protein-BP (CREBBP) (50–60% of the cases) or the homologous gene E1A-binding protein (EP300) (5%) are involved in RTS. RTS patients show intellectual disability, distinctive clinical characteristics (such as broad and sometimes laterally deviated thumbs and halluces), short stature, and craniospinal and posterior fossa abnormalities. We describe the case of a girl delivered at term with mild perinatal asphyxia. At birth, weight and length were 2630 g ( 1 73 SDS) and 47 5 cm ( 1 34 SDS), respectively. A clinical diagnosis of RTS was performed in the first days of life because of broad thumbs and toes, downslating palpebral fissures and malpositioned ears with dysplastic helices. The molecular analysis showed a frameshift mutation of the CREBBP gene due to a duplication of 20 nucleotides (c.5838_5857dup20). This mutation, never described before, involves the exon 31 of the CREBBP gene and leads to a stop codon (p.Pro1953HisfsX30) with a resulting truncated protein of 1982 aminoacids (the wild-type protein is of 2442 aminoacids). In the following years, she showed growth impairment and development delay. She was referred to our attention at the age of 3 years because of short stature (86 5 cm, 2 1 SDS, 25–50° percentile following RTS growth charts). The growth velocity in the last year was 5 69 cm/year ( 1 67 SDS). The weight was between 10° and 25° percentile (between 25 and 50°pc following RTS growth charts). Tanner pubertal stage was Ph1 B1, and the bone age showed a delay of 2 years. Clinical examination showed features consistent with RTS and cutaneous neuromas. Cortisol levels at 8:00 a.m., thyroid, hepatic and renal functions were normal. Two arginine provocative tests for growth hormone (GH) secretion were performed. GH peak levels were 5 57 lg/l and 6 69 lg/l (n.v. >10 lg/l), respectively, revealing a GH deficiency. The IGF-1 levels were 22 27 nmol/l (n.v. 13 88– 32 75 nmol/l). A brain magnetic resonance (MRI) showed normal pituitary height (3 8 mm with a normal height range for age and sex of 4 25 0 68 mm) and volume, normal anatomy of the stalk, normal position of the posterior pituitary, and normal anatomy of the hypothalamic region. A thinning of the corpus callosum was evident. She started GH therapy (0 033 mg/kg/day) when she was 3 5 years old, with good improvement of growth velocity (the patient’s growth charts are shown in Fig. 1a and b). At last follow-up, the patient was 9 9 years old and her stature was 134 6 cm (+0 58 SDS according Italian charts and 90–97°percentile according RTS growth charts). At the present time, the GH dose is 0 022 mg/kg/day with a growth velocity of 6 95 cm/year (+1 90 SDS). Pubertal stage is Ph1 B1. IGF-1 levels are 49 38 nmol/l (n.v. 16 50–34 19 nmol/l). The bone age shows a retardation of 16 months. The thyroid function is normal. TSH levels are 3 35 mIU/l (n.v. 0 27–4 20 mIU/l), Ft4 levels are 13 64 pmol/l (n.v. 11 9–21 8 pmol/l), and Ft3 levels are 0 059 pmol/l (n.v. 0 027–0 070 pmol/l). She did not presented any side effects to GH therapy. In individuals with RTS, short stature is considered a classic feature of the syndrome and indirect measures of growth hormone secretion have been usually reported as normal. Therefore, these patients do not usually undergone dynamic testing to detect growth hormone deficiency. In literature, we found a single case report of RTS female patient with GH deficiency associated with a CREBBP frameshift mutation. The diagnosis of GH deficiency was performed when she was 11 years old. She was treated with GH therapy for 5 years with good improvement in growth velocity (reaching the 3° percentile of height for the normal population growth chart and the 75° percentile of height for the RTS growth chart) without any side effects. Interestingly, this patient presented also pituitary hypoplasia, Arnold Chiari malformation type 1 and double syringomyelic cavity. This fact underlines the possibility that GH deficiency could play a role in the short stature of RTS patients with CREBBP mutation and that the replacement therapy could lead to improvement of stature. Another RTS patient with GH deficiency and short stature is present in the population of Spena et al. and this patient showed a frameshift CREBBP mutation leading to a stop codon at aminoacid 107. Unfortunately, no more auxological data and information about a possible therapy are available. Herein, we report a precocious diagnosis of GH deficiency (performed when the patient was 3 5 years old) associated with a new CREBBP mutation. Our case report shows a GH replacement therapy started early in life in RTS patients with GH deficiency leading to an important improvement of stature (her height reached the 25° percentile according normal population and 90–97° percentile according RTS growth charts) without any side effects. Unlike the patient previously described, our patient did not present pituitary hypoplasia. The hypothesis of the linkage between short stature and GH deficiency in RTS patients with CREBBP mutations is supported by previous studies in mice and in vitro. cAMP-response element-binding protein (CREB) is one of the first transcription factors that showed an impact on somatic growth. CREB is required for the efficient production of GHRH in hypothalamus and GH in pituitary gland. In fact, CREBmutant mice present reduced postnatal growth consistent with dwarfism caused by GH deficiency. CREBBP, involved in RTS pathogenesis, is a nuclear factor named for its ability to bind CREB. It is possible that CREBBP mutations affect the CREB–CREBBP interaction, determining an impaired CREB-binding protein both at hypothalamic and at pituitary level, with consequent reduction in GH levels. In addition, at pituitary level, CREBBP interacts as cofactor with Pit-1. Pit-1 is an important transcription factor that promotes growth hormone and stimulates somatic growth. Therefore, an impairment of CREBBP/Pit-1 interaction could affect pituitary GH secretion. Considering all the GH secretion steps in whom CREBBP could be implicated, we suppose that in RTS patients without

Neumomediastino grave y mutación del gen ABCA3 en un niño: una relación enigmática

A 4-year-old boy was admitted due to an episode of acute febrile respiratory infection characterized by rhinitis and cough. The patient presented intense dyspnea, tachypnea (60 breaths per minute), bilateral reduction in the vesicular murmur and diffuse crackles. Oxygen saturation (SaO2) while using 4 l/min of O2 was 93%, and no response at all was observed to treatment with inhaled beta agonists. The patient was administered clarithromycin, amoxicillin–clavulanic acid and dexamethasone, but his state quickly worsened with increased respiratory effort and the appearance of subcutaneous emphysema. The patient was transferred to the intensive care unit of our pediatric hospital. The child had been born full term with no postnatal complications. He had been completely healthy up until this episode and had no family history of respiratory diseases. Upon examination, the patient continued to present dyspnea, and SaO2 was 92% with 7 l/min of O2. Laboratory analysis showed mild anemia (10.3 g/dl) and a high leukocyte count (18.470/mm3 with 70% of neutrophils). The C-reactive protein, immunoglobulin levels, electrolytes in blood, serum creatinine and liver function tests were normal. Thoracic radiography revealed thickening of the interstitial pattern, multiple radiotransparent areas due to the interstitial emphysema and parenchymatous opacities in the left middle and lower lung fields. Thoracic computed tomography revealed diffuse pneumomediastinum with subcutaneous emphysema (Fig. 1). A central venous catheter was inserted for the nutritional support of the patient and for the management of the intravenous treatment. The oxygen supply was maintained at the same time that antibiotic, antifungal, antiviral and anti-inflammatory (high doses of corticosteroids and intravenous immunoglobulin)

Higher growth, fat and fat-free masses correlate with larger cerebellar volumes in preterm infants at term

Smaller cerebellar volumes in very low‐birthweight (VLBW) infants at term have been related to adverse cognitive outcomes, and this study evaluated whether these volumes were associated with a growth in body composition during hospital stays.

Acute lobar nephritis in children: Not so easy to recognize and manage

Acute lobar nephritis (ALN) is a localized non-liquefactive inflammatory renal bacterial infection, which typically involves one or more lobes. ALN is considered to be a midpoint in the spectrum of upper urinary tract infection, a spectrum ranging from uncomplicated pyelonephritis to intrarenal abscess. This condition may be difficult to recognize due to the lack of specific symptoms and laboratory findings. Therefore the disease is probably underdiagnosed. Computed tomography scanning represents the diagnostic gold standard for ALN, but magnetic resonance imagine could be considered in order to limit irradiation. The diagnosis is relevant since initial intravenous antibiotic therapy and overall length of treatment should not be shorter than 3 wk. We review the literature and analyze the ALN clinical presentation starting from four cases with the aim to give to the clinicians the elements to suspect and recognize the ALN in children.